Oxitec’s Genetically Modified Mosquitoes: Ongoing Concerns August 2012 UK biotech company Oxitec has released millions of genetically modified (GM) mosquitoes in Brazil, following smaller experiments in the Cayman Islands and Malaysia. Further experiments are planned in Brazil on an even larger scale. The company also hopes to conduct experimental releases in Panama, the USA (Florida Keys), India, Sri Lanka and perhaps other countries. Oxitec’s patented technique for genetically modifying insects is known as RIDL (Release of Insects carrying a Dominant Lethal genetic system). 1 All the company’s open field experiments to date involve its OX513A strain of the Aedes aegypti mosquito, which is genetically engineered to contain a red fluorescent marker and the RIDL ‘conditional lethality’ trait. Oxitec’s male OX513A GM mosquitoes are intended to mate with wild females and produce offspring which die as larvae. Releases of large numbers of GM males, vastly outnumbering the wild male mosquito population, are intended to reduce the total adult population of mosquitoes over time, as many of the GM offspring fail to survive to adulthood. The GM mosquitoes released in the experiments are Yellow Fever mosquitoes ( Aedes aegypti ) which transmit the tropical disease dengue fever. No risk assessment was published for public scrutiny or consultation prior to releases of GM mosquitoes in the Cayman Islands or Brazil. In Malaysia only a summary was published. GeneWatch has obtained copies of the risk assessments in the UK because they must be provided by Oxitec when exporting GM mosquito eggs for open release for the first time to a given country. In no case did the company correctly follow this notification procedure, with the result that there was no independent scrutiny of whether these risk assessments met the required European standards. There remain many concerns about Oxitec’s technology. Some unanswered questions are highlighted below. Issues include: • The results of Oxitec’s population suppression experiments in Cayman and Brazil have not been published in scientific journals, but information in the public domain suggests that RIDL may not be particularly effective at suppressing mosquito populations and could even be less, not more, effective than the Sterile Insect Technique (SIT) using irradiated insects. • Ineffectiveness is a matter of particular concern in dengue endemic areas because in some situations partial or temporary suppression of mosquito populations could make the dengue situation worse. • Oxitec did not correctly follow the procedure for transboundary notification of shipments of GM mosquito eggs overseas: the practical consequence of this is that risk assessments were not made publicly available prior to open release trials and did not meet the necessary standards. • Numerous important issues were therefore not properly considered before millions of GM mosquitoes were released in to the environment in the Cayman Islands and 1 GeneWatch UK Briefing August 2012 Brazil. Smaller experiments in Malaysia did include a consultation process, however there were some deficiencies with the process which need to be addressed. • In its publicity about the trials, Oxitec has oversimplified the complex relationship between Aedes aegypti mosquitoes, other mosquito species, the humans that are bitten, and the four serotypes of dengue virus. This means that most potential adverse impacts have effectively been excluded from public debate, the risk assessment process, and the process of seeking consent from local populations. • Oxitec has repeatedly referred to its GM mosquitoes as sterile, when this so-called sterility is partial and conditional. The GM mosquitoes do breed and most die at the larval stage: the extent to which their offspring survive to adulthood is one of many factors which influences the efficacy and safety of this approach. • The decision to scale-up experiments in Brazil appears to be driven by a political agreement to commercialise Oxitec’s technology there, rather than by a thorough assessment of the likely risks and benefits. Will releasing GM mosquitoes suppress wild mosquito populations? Oxitec frequently compares its RIDL technology to the Sterile Insect Technique (SIT). SIT involves releasing large numbers of irradiated insects to mate with wild ones. Since the irradiated insects are sterile, no offspring are produced and this can be effective in reducing insect populations. Chemical methods of sterilisation have also been tested. SIT has been used successfully with some agricultural pest species, but has been less successful with others because different insect species have very different life histories and behaviours.2 In general SIT is not effective at reducing high density populations of insects without first using other conventional approaches to reduce the population, but it may be effective at reducing or eradicating smaller, isolated populations. 3 However, SIT has not generally been successful for mosquitoes, where population suppression has been achieved only in a few experiments with very large “release ratios” of sterile to wild mosquitoes.4,5 Although there have been a number of field trials of mating fitness and other factors, only two population suppression trials have been conducted using SIT for Aedes aegypti mosquitoes. These took place during the late 1970s in an isolated Kenyan village, using semi-sterile males which had a fertility of 37%. In the first experiment, the estimated release ratio of about ten to one (released to wild males) had only a small effect on population levels and was ineffective compared to removing larvae from domestic water containers in a neighbouring village. 6 A second SIT experiment was conducted a little later in the same locality with similar results.7 Two genetic markers that were carried by released males but unknown to the region persisted in the population during the entire period of observation of nearly a year after the experiments. 8 SIT is not currently in use for any species of mosquito, however there are current research programmes investigating the potential use of SIT using irradiated Anopheles arabiensis mosquitoes (which transmit malaria) in Sudan 9; and irradiated Aedes albopictus mosquitoes (which transmit dengue and other viruses) in Italy.10 Recent experiments with Aedes albopictus suggest that it is possible to adjust radiation doses so that these mosquitoes are sterilised without significant loss of mating fitness. 11 Applying SIT to mosquitoes is complicated by what scientists call “density dependent” effects on mosquito populations.12,13 The size of a population of mosquitoes does not depend only on how well the mosquitoes reproduce but also on other factors such as competition for food between larvae and for breeding sites. Reducing reproductive fitness may have little effect if the size of the mosquito population is limited mainly by these factors, rather than by its ability to reproduce. 14 Density dependent effects mean that reducing the numbers of mosquitoes that breed successfully can sometimes have little effect on total numbers of adult mosquitoes and paradoxically might sometimes even increase populations: for example, because reducing breeding success also reduces competition between larvae for resources, 2 GeneWatch UK Briefing August 2012 resulting in increased survival rates or a rebound in numbers. Density dependent effects can influence the current generation of mosquitoes or only affect future generations (delayed density-dependent effects). 15 Density dependent effects tend to be less important for agricultural pests in large-scale monoculture agriculture, because their food supplies are effectively unlimited, so competition for resources can play a less important role. Influx of mosquitoes from neighbouring areas into an area where the population is suppressed can be a major problem with the use of SIT. Incomplete sterilization, reduced mating competitiveness (compared to wild mosquitoes) and immigration of mosquitoes from surrounding areas can all reduce the effectiveness of SIT. 16 Aedes aegypti eggs can survive several months under dry conditions in a dormancy state at the end of their embryonic development and this adds to the difficulties of controlling populations, which can spread through dispersal of the eggs. 17 The US Centers for Disease Control and Prevention (CDC) suggests that even if all larvae, pupae, and adult Aedes aegypti were to be eliminated at once from a site, its population could recover two weeks later as a result of egg hatching following rainfall or the addition of water to containers harbouring eggs. 18 Oxitec argues that RIDL will be more successful for mosquitoes than SIT for two main reasons: (1) RIDL males will be fitter than irradiated ones and will compete more successfully with wild males to mate with wild females; and (2) because the offspring of the GM mosquitoes survive to the late-larval or early-pupal stage, they will also compete with wild larvae for food, further supressing the wild mosquito population. Oxitec makes these predictions based on a number of computer models which aim to forecast how mosquito populations will respond to large-scale releases of its GM mosquitoes. 19,20,21,22 These models all contain many simplifying assumptions, including assumptions about how density dependence affects the population of mosquitoes. These computer models build on a model built using data on the development of adult and larvae Aedes aegypti mosquitos in Thailand 23 : they have